1.Dietary flavonoid fisetin for cancer prevention and treatment.
Lall RK1,2, Adhami VM2, Mukhtar H2. Mol Nutr Food Res. 2016 Apr 5. doi: 10.1002/mnfr.201600025. [Epub ahead of print]
Cancer remains a major public health concern and a significant cause of death worldwide. Identification of bioactive molecules that have the potential to inhibit carcinogenesis continues to garner interest among the scientific community. In particular, flavonoids from dietary sources are the most sought after because of their safety, cost-effectiveness and feasibility of oral administration. Emerging data has provided newer insights into understanding the molecular mechanisms that are essential to identify novel mechanism-based strategies for cancer prevention and treatment. Dietary flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) found in many fruits and vegetables has been shown in preclinical studies to inhibit cancer growth through alteration of cell cycle, inducing apoptosis, angiogenesis, invasion and metastasis without causing any toxicity to normal cells. Although data from in-vitro and in-vivo studies look convincing, well designed clinical trials in humans are needed to conclusively determine the efficacy across various cancers.
2.Paclitaxel and the dietary flavonoid fisetin: a synergistic combination that induces mitotic catastrophe and autophagic cell death in A549 non-small cell lung cancer cells.
Klimaszewska-Wisniewska A1, Halas-Wisniewska M1, Tadrowski T2, Gagat M1, Grzanka D2, Grzanka A1. Cancer Cell Int. 2016 Feb 16;16:10. doi: 10.1186/s12935-016-0288-3. eCollection 2016.
BACKGROUND: The use of the dietary polyphenols as chemosensitizing agents to enhance the efficacy of conventional cytostatic drugs has recently gained the attention of scientists and clinicians as a plausible approach for overcoming the limitations of chemotherapy (e.g. drug resistance and cytotoxicity). The aim of this study was to investigate whether a naturally occurring diet-based flavonoid, fisetin, at physiologically attainable concentrations, could act synergistically with clinically achievable doses of paclitaxel to produce growth inhibitory and/or pro-death effects on A549 non-small cell lung cancer cells, and if it does, what mechanisms might be involved.
3.Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice.
Ahmad A1, Ali T1, Park HY2, Badshah H1, Rehman SU1, Kim MO3. Mol Neurobiol. 2016 Mar 5. [Epub ahead of print]
Alzheimer's disease (AD) is a devastating and progressive neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta (Aβ) and the hyperphosphorylation of tau proteins in the brain. The deposition of Aβ aggregates triggers synaptic dysfunction, hyperphosphorylation of tau, and neurodegeneration, which lead to cognitive disorders. Here, we investigated the neuroprotective effect of fisetin in the Aβ1-42 mouse model of AD. Single intracerebroventricular injections of Aβ1-42 (3 μl/5 min/mouse) markedly induced memory/synaptic deficits, neuroinflammation, and neurodegeneration. Intraperitoneal injections of fisetin at a dose of 20 mg/kg/day for 2 weeks starting 24 h after Aβ1-42 injection significantly decreased the Aβ1-42-induced accumulation of Aβ, BACE-1 expression, and hyperphosphorylation of tau protein at serine 413. Fisetin treatment also markedly reversed Aβ1-42-induced synaptic dysfunction by increasing the levels of both presynaptic (SYN and SNAP-25) and postsynaptic proteins (PSD-95, SNAP-23, p-GluR1 (Ser 845), p-CREB (Ser 133) and p-CAMKII (Thr 286) and ultimately improved mouse memory, as observed in the Morris water maze test.